RNA and ATAC mutual sequencing (RAM-seq) for simultaneous single-cell transcriptome and chromatin profiling
This technology is a multiplex single-cell sequencing workflow that simultaneously profiles RNA expression and chromatin accessibility at high depth within individual cells.
Unmet Need: Affordable, instrument free joint single-cell RNA and chromatin profiling
Single-cell multi-omics is essential for resolving cellular heterogeneity and the regulatory mechanisms behind disease and therapeutic response. Existing workflows that simultaneously measure transcriptome and chromatin accessibility depend on dedicated microfluidic instruments that are costly to acquire and operate. Furthermore, existing methods use inefficient chemistry that produces poor-quality reads, much of which is thrown out during quality checks, pushing up the cost per cell. These barriers limit access for smaller research groups and constrain the scale at which biopharma can run discovery campaigns.
The Technology: Plate-based dual RNA/ATAC profiling
This technology is a single-cell sequencing workflow that simultaneously profiles RNA expression and chromatin accessibility (ATAC) sequencing without dedicated microfluidic instruments. Single cells are sorted into individual microwell plate wells, where both RNA transcripts and tagmented chromatin fragments are captured using a commercially available template-switching reverse transcriptase and tagged with well-specific barcodes. Pooled libraries are then amplified and sequenced using standard sequencing platforms, with the scalability down to as few as 96 cells per run. By eliminating the need for specialized third-party library preparation instruments and enabling processing directly in a microwell plate, this approach simplifies workflow and improves retention of 90% of cells passing quality control filtering. This platform is also compatible with ERCC spikes-ins and downstream analytical pipelines, without requiring chemical or physical partitioning prior to amplification.
Applications:
Joint single-cell transcriptome and chromatin accessibility profiling
Multiplexed single-cell analysis of transcriptome, chromatin accessibility, and cell-surface markers
Characterization of therapeutic mechanism of action
Standalone single-cell RNA-seq or ATAC-seq library generation
Advantages:
Eliminates the need for dedicated microfluidic single-cell instrumentation
Reduces per-cell sequencing cost relative to ligation-based workflows
Improves read quality through template-switching reverse transcription
Compatible with major sequencing platforms
Integrates with existing plate-based laboratory equipment and reagents
Lead Inventor:
Patent Information:
Patent Pending (US 20240093183)
Related Publications:
Tech Ventures Reference:
- Licensing Contact: Joan Martinez